The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy - A randomized, double-blind, placebo-controlled trial

Epilepsy Behav. 2018 Oct;87:32-38. doi: 10.1016/j.yebeh.2018.08.016. Epub 2018 Aug 28.


Objectives: The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated.

Methods: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n = 99) subjects with DRE, aged 5-16 years (n = 85) and 17-45 years (n = 14). After randomization, subjects were given two, four, or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n = 33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n = 33), or placebo (high oleic acid sunflower oil, n = 33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio (IRR) were tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure, and number of antiepileptic drug (AED) combinations used at enrollment.

Results: Fifty-nine subjects (n = 59) completed the study (59.6%). The average number of seizures per month were 9.7 ± 1.2 in the EPA group, 11.7 ± 1.5 in the DHA group, and 16.6 ± 1.5 in the placebo group. Age, gender, and seizure-type adjusted seizure IRRs of the EPA and DHA groups compared with the placebo group were 0.61 (CI = 0.42-0.88, p = 0.008, 42% reduction) and 0.67 (CI = 0.46-1.0, p = 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p = 0.56). Both treatment groups had a significantly higher number of seizure-free days compared with the placebo group (p < 0.05).

Significance: This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE.

Keywords: Antiepileptic drugs (AEDs); Omega-3 fatty acids; Seizure incidence rate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Child
  • Child, Preschool
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / pharmacology*
  • Double-Blind Method
  • Drug Combinations
  • Drug Resistant Epilepsy / drug therapy*
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / pharmacology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Young Adult


  • Anticonvulsants
  • Drug Combinations
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data

  • ISRCTN/ISRCTN80844630